Annona muricata Leaves Extract Inhibit Carcinogenesis and Regulates Inflammatory Responses in AOM/DSS-Induced Colitis-Associated Carcinogenesis Mice

Indrawati, Lili and Kusmardi, Kusmardi and Gultom, Fajar Lamhot and Sani, Yulvian (2024) Annona muricata Leaves Extract Inhibit Carcinogenesis and Regulates Inflammatory Responses in AOM/DSS-Induced Colitis-Associated Carcinogenesis Mice. The Indonesian Journal of Gastroenterology, Hepatology and Digestive Endoscopy, 25 (2). pp. 309-318. ISSN 2302-8181

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Abstract

Background: Colon cancer is a major public health problem. The present study was conducted to determine the inhibitory effect of Annona muricata leaves on carcinogenesis and inflammation in the colorectal preneoplasia development of mice. Methods: The study was experimental research that conducted in Faculty of Medicine Universitas Indonesia. The effect of Ethanol Insoluble Fraction of Annona muricata water extract (EIFAM) was examined on the preneoplastic lesions. EIFAM was administered orally in three different doses (200 mg/kgBW (low dose), 400 mg/kgBW (medium dose), and 800 mg/kgBW (high dose)) in each group of mice per day until the mice were terminated. The expression of Caspase, COX-2, and β-catenin were observed in the epithelial cells of colon mucosa crypts. Analysis of the data was done using the ANOVA method. Results: Histological assessment using Hematoxylin Eosin Staining was done in a blinded fashion to avoid bias. Our results indicate that multiple organ dysplasia was induced with azoxymethane (AOM) in male Swiss Webster mice. The effect of A. muricata extract administration showed significant result only on heart. The activity of caspase showed no significant effect on all organs when treated with the extracts as compared to untreated group. The effects of the extract on various organs’ inflammatory markers varies. COX-2 lowering effect of high doses is significant in the liver. The medium dose has significant catenin lowering effect on jejenum, colon, and brain. While the medium and high dose have significant catenin lowering effect on duodenum, heart, and kidney respectively. Conclusions: Ethanol-insoluble fraction of Annona muricata (EIFAM) leaves water extract has a potential inhibitory effect of Annona muricata leaves on carcinogenesis and inflammation in the colorectal preneoplasia development of mice. Keywords: Apoptosis, Dysplasia, β-Catenin, COX-2, Colorectal cancer, caspase

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